Ozone interaction with rodent lung. II. Effects on oxygen consumption of mitochondria

Mohammad G. Mustafa, Anthony J. DeLucia, George K. York, Christopher Arth, Carroll E Cross

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

In order to examine oxidant effects on lung cellular oxidative metabolism, mitochondrial O2 consumption (substrate oxidation) was studied in the lungs of O3-exposed animals. Male rats (60 to 90-day-old) were exopsed to O3 either acutely (2 p.p.m. for 8 hours) or subacutely (0.8 p.p.m. for 10 to 20 days). For in vitro experiments suspensions of rat lung homogenates or rat lung mitochondria were exposed to a flow of 10 to 15 p.p.m. O3 per minute for 20 minutes; both homogenate and mitochondrial preparations absorbed O3 at a rate of 2.3 to 5.0 p.p.m. per minute (depending upon the amount of tissue). A total of 30 to 40 nmoles O3 per milligram of protein was absorbed during this period. Subsequent to acute exposures, the rate of O2 consumption (oxidation of succinate) in lung homogenate or mitochondrial fraction decreased approximately 25 per cent (p < 0.02) relative to control rats. Under in vitro conditions, the depression of respiration was 23 per cent (p < 0.001) for homogenate and 45 per cent (p < 0.001) for mitochondria. In contrast to the effects of acute O3 exposures, subacute exposures resulted in an augmentation of lung cellular O2 utilization. As high as 45 per cent (p < 0.02) stimulation of O2 consumption occurred in homogenates of subacutely exposed rat lungs compared to those of control rat lungs. The specific activity (e.g., succinate oxidase activity per milligram protein) in the isolated mitochondral fraction was only 15 per cent (p < 0.05) higher in the lungs of exposed rats compared to those of control rats, thus failing to account for the over-all stimulation of mitochondrial respiration observed in exposed rat lungs. Examination of lung sections by transmission electron microscopy revealed a 3-fold greater abundance (p < 0.01) of large alveolar (Type II) cells in exposed rat lungs compared to control rat lungs. Since Type II cells contain numerous mitochondria, their proliferation is likely to increase the over-all population of mitochondria in the lung, thus contributing significantly to the respiratory augmentation observed in exposed rat lungs. Lung mitochondrial respiratory activity may serve as a biochemical index for possible changes of cellular constituency in the lung following chronic oxidant exposure.

Original languageEnglish (US)
Pages (from-to)357-365
Number of pages9
JournalThe Journal of Laboratory and Clinical Medicine
Volume82
Issue number3
StatePublished - 1973

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

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